The proposed research represents a multidisciplinary approach to problems in allograft and tumor immunity as they relate to specific adoptive immunotherapy for the treatment of advanced cancer. The main focus of the research will be on the study of factors influencing specific sensitization of donor immunocompetent cells against antigens present on the surface of malignant cells. The studies will be conducted in AKR mice bearing Gross virus-associated spontaneous leukemia-lymphoma. Virion structural antigens, virus-induced cell surface antigens, minor histocompatibilty antigens and xenogeneic cross-reactive leukemia associated antigens will be evaluated as immunogens for specific adoptive immunotherapy. In an attempt to minimize the complication of graft-versus-host disease, strains of mice that are allogeneic, but matched with AKR at the H-2 major histocompatibility genetic locus will be used as donors of immunocompetent cells. Both in vivo and in vitro sensitization techniques will be investigated as methods to manipulate donor immunocompetent cells for specific adoptive immunotherapy. The effect of sensitization of histocompatible immunocompetent cells on antileukemic reactivity and antihost reactivity will be assayed in vivo. Sensitized cells manifesting marked antileukemic and minimal antihost reactivity will be used in combination with chemoradiotherapy for adoptive immunotherapy of AKR mice bearing advanced spontaneous leukemia-lymphoma. We are hopeful that insights gained in these studies of principles regulating the generation of specifically sensitized cytotoxic effector cells in histocompatible donors will help elucidate successful approaches to the immunotherapy of malignancy in man.